BERING: Binimetinib Plus Encorafenib Real Life Investigation of Next Generation Melanoma Treatment

• Sponsor: Pierre Fabre Pharma GmbH (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04045691
• Collaborator: Pierre Fabre Pharma Austria (Other), Pierre Fabre Pharma AG (Industry)
• Enrollment: 750
• Locations: 59
• Anticipated Duration (Months): 94.5
• Patients Per Site: 12.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

BERING-MELANOMA - designed as a prospective, longitudinal, non-interventional study - investigates real-world effectiveness, quality of life, safety and tolerability of encorafenib plus binimetinib in unresectable advanced or metastatic BRAF(Rapidly Accelerated Fibrosarcoma isoform B)-V600-mutant malignant melanoma after commercial availability of these two products in Germany, Austria and Switzerland. The study focusses on the documentation of the first and second line setting (i.e. after one line of prior checkpoint inhibition) by documenting patients treated according to the SmPC (Summary of Product Characteristics).

Condition or Disease	Intervention/Treatment	Phase
Melanoma Stage IV; Melanoma Stage III	Drug: Encorafenib; Drug: Binimetinib

Study Design

• Study Type: Observational
• Anticipated Enrollment: 750 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Encorafenib Plus Binimetinib in Patients With Locally Advanced, Unresectable or Metastatic BRAFV600-mutated Melanoma: a Multi-centric, Multinational, Prospective, Longitudinal, Non-interventional Study in Germany, Austria and Switzerland - BERING MELANOMA
• Actual Study Start Date: Oct 17, 2019
• Anticipated Primary Completion Date: Dec 1, 2026
• Anticipated Study Completion Date: Sep 1, 2027

Outcome Measures

Primary Outcome Measures

1. Progression-free survival [At 12 months after start of treatment]

   Progression-free survival rate

Secondary Outcome Measures

1. Patient and disease profiles at start of treatment with encorafenib plus binimetinib [Baseline]

   Demographic and disease characteristics

2. Type of treatments before and after encorafenib plus binimetinib [Complete observation time-frame (the total observation period of this study will amount to 90 months).]

   Treatment sequence prior to and after encorafenib plus binimetinib; by documenting pre-treatments with adjuvant therapy and systemic therapy in palliative setting; and by documenting subsequent systemic treatment lines after administration of encorafenib plus binimetinib

3. Sequence of treatments before and after encorafenib plus binimetinib [Complete observation time-frame (the total observation period of this study will amount to 90 months).]

   Treatment sequence prior to and after encorafenib plus binimetinib; by documenting pre-treatments with adjuvant therapy and systemic therapy in palliative setting; and by documenting subsequent systemic treatment lines after administration of encorafenib plus binimetinib

4. Characteristics of treatment with encorafenib plus binimetinib [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

   Evaluation of reason for treatment selection (efficacy, safety profile, quality of life, patients preference, physician's preference, comorbidities, other)

5. Effectiveness of treatment with encorafenib plus binimetinib [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

   Further progression-free survival parameters

6. Effectiveness of treatment with encorafenib plus binimetinib [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

   Time-to-progression

7. Effectiveness of treatment with encorafenib plus binimetinib [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

   Best observed tumor response

8. Effectiveness of treatment with encorafenib plus binimetinib [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

   Overall response rate

9. Effectiveness of treatment with encorafenib plus binimetinib [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

   Duration of response

10. Effectiveness of treatment with encorafenib plus binimetinib [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

    Disease control rate

11. Effectiveness of treatment with encorafenib plus binimetinib [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

    Duration of disease control

12. Effectiveness of treatment with encorafenib plus binimetinib [Complete observation time-frame (the total observation period of this study will amount to 90 months).]

    Overall survival

13. Patient reported outcomes during treatment with encorafenib plus binimetinib - evaluated with EORTC QLQ C-30 [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

    EORTC QLQ C-30 questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life C-30 questionnaires) to assess quality of life of cancer patients; comprises 30 items, 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. The remaining six single-item (dyspnoea, appetite loss, sleep disturbance, constipation, diarrhoea and the financial impact) scales assess symptoms.

14. Patient reported outcomes during treatment with encorafenib plus binimetinib evaluated with WPAI [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

    WPAI questionnaires (Work Productivity and Activity Impairment questionnaires). The following questions ask about the effect of patients melanoma on the ability to work and perform regular activities. Are you currently employed (working for pay)? During the past seven days, how many hours did you miss from work because of problems associated with your melanoma? During the past seven days, how many hours did you miss from work because of any other reason? During the past seven days, how many hours did you actually work? During the past seven days, how much did your melanoma affect your productivity while you were working? During the past seven days, how much did your melanoma affect your ability to do your regular daily activities, other than work at a job?

15. Patient reported outcomes during treatment with encorafenib plus binimetinib evaluated with CTSQ [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

    CTSQ questionnaires (Cancer Therapy Satisfaction Questionnaire) to assess patients' opinions and feelings concerning their cancer therapy and associated adverse events: Questions to patients thoughts about cancer therapy (IV/pills). Scale: [Always, Most of the time, Some-times, Rarely, Never]; Questions to patients satisfaction with the most recent cancer therapy (IV/pills): Scale reg. benefit: [Much better than my expectations Somewhat better than my expectations, Met my expectations, Somewhat worse than my expectations, Much worse than my expectations]; Scale reg. side effects: [Much better than I expected, Somewhat better than I expected, Exactly as I expected, Somewhat worse than I expected, Much worse than I expected]; Scale reg. satisfaction: [Very satisfied, Satisfied, Neither satisfied nor dissatisfied, Dissatisfied, Very dissatisfied]; Scale reg. choice of therapy: [Yes, definitely, Probably Yes, I don't know, Probably not, Definitely not]

16. Physicians' satisfaction with regard the treatment with encorafenib plus binimetinib [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

    Physicians' satisfaction questionnaires (measuring Physician's Satisfaction with regard to Effictiveness and Safety, as well as Physician's Overall Treatment Satisfaction) using the following scale construct: Physician's Satisfaction with regard to Efficiency Physician's Satisfaction with regard to Safety Physician's Overall Treatment Satisfaction Scale: very dissatisfied dissatisfied moderately satisfied satisfied very satisfied

17. Safety and tolerability of treatment with encorafenib plus binimetinib - Adverse events and adverse reactions including time to onset and time to resolution [Complete observation time-frame (the total observation period of this study will amount to 90 months).]

    Number of patients with Adverse Events and maximum grade per patient, Adverse Drug Reactions, Adverse Drug Reactions grade 3/4, Serious Adverse Events, Serious Adverse Drug Reactions.

18. Prognostic factors [Complete observation time-frame (the total observation period of this study will amount to 90 months).]

    Influence of prognostic factors on quality of life outcome parameters

19. Prognostic factors [Complete observation time-frame (the total observation period of this study will amount to 90 months).]

    Influence of prognostic factors on effectiveness

20. Prognostic factors [Complete observation time-frame (the total observation period of this study will amount to 90 months).]

    Influence of prognostic factors on safety

21. Treatment duration [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

    From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last)

22. Treatment dose intensity [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

    From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last)

23. Number of treatment interruptions [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

    From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last)

24. Duration of treatment interruptions [From start to end of treatment (anticipated median treatment duration ca. 12 months)]

    From date of first treatment (encorafenib or binimetinib, whichever occurs first) until date of last treatment (encorafenib or binimetinib, whichever occurs last)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent of the patient with regard to the pseudonymized documentation as well as the transfer and processing of his/her data within the study and the ADOREG [Cancer Registry of German Working Group of Dermato-Oncology] registry (data transfer to ADOREG registry only for patients from German sites);

• Legally capable male or female patient ≥ 18 years of age (no upper limit);

• Decision was taken to treat the patient with encorafenib plus binimetinib in accordance with the current SmPC [Summary of Product Characteristics] and by prescription; this decision was taken prior to and independent from the inclusion into the study;

• Treatment with encorafenib plus binimetinib has been started ≤ 6 months prior to providing written informed consent for this study or is planned to be started in the near future;

• Unresectable advanced or metastatic malignant melanoma with BRAF [Rapidly Accelerated Fibrosarcoma isoform B] V600 mutation;

• Treatment-naive or after one prior line of checkpoint inhibitor treatment (anti-CTLA4 [Cytotoxic T-Lymphocyte Antigen-4] and/or anti-PD(L)1 [Programmed cell Death protein 1]) in the unresectable advanced or metastatic setting.

Exclusion Criteria:

• Previous treatment with a BRAF- and/or MEK [Mitogen-Activated

Protein/Extracellular-signal Regulated Kinase]- inhibitor except for:

-- prior adjuvant treatment with BRAF+MEK-inhibitor combination therapy that ended > 6 months prior start of Encorafenib/Binimetinib treatment;

• More than one prior line of checkpoint inhibitor treatment in the unresectable advanced or metastatic setting;

• Any previous chemotherapeutic treatment of the melanoma disease;

• Presence of any contraindication with regard to the encorafenib-binimetinib-treatment as specified in the corresponding SmPCs;

• Current or upcoming participation in an interventional clinical trial;

• Current or upcoming systemic treatment of any other tumor than melanoma;

• Prisoners or persons who are compulsorily detained (involuntarily incarcerated).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	11	Graz		Austria
2	13	Innsbruck		Austria
3	14	Klagenfurt		Austria
4	10	Linz		Austria
5	3	Linz		Austria
6	12	Salzburg		Austria
7	23	Wiener Neustadt		Austria
8	22	Wien		Austria
9	53	Wien		Austria
10	45	Ahaus		Germany
11	8	Aschaffenburg		Germany
12	56	Augsburg		Germany
13	51	Berlin		Germany
14	27	Bremerhaven		Germany
15	1	Buxtehude		Germany
16	43	Chemnitz		Germany
17	34	Donauwörth		Germany
18	49	Dresden		Germany
19	47	Duisburg		Germany
20	40	Erfurt		Germany
21	20	Essen		Germany
22	9	Gera		Germany
23	28	Gießen		Germany
24	42	Goslar		Germany
25	59	Göttingen		Germany
26	19	Hamburg		Germany
27	21	Hannover		Germany
28	2	Heidelberg		Germany
29	33	Karlsruhe		Germany
30	39	Kiel		Germany
31	29	Landshut		Germany
32	44	Leipzig		Germany
33	30	Ludwigshafen		Germany
34	4	Lübeck		Germany
35	46	Magdeburg		Germany
36	15	Mainz		Germany
37	5	Mannheim		Germany
38	57	Marburg		Germany
39	6	Minden		Germany
40	31	München		Germany
41	7	München		Germany
42	16	Münster		Germany
43	35	Münster		Germany
44	18	Nürnberg		Germany
45	50	Regensburg		Germany
46	41	Schorndorf		Germany
47	17	Schwerin		Germany
48	48	Stolberg		Germany
49	55	Trier		Germany
50	54	Tübingen		Germany
51	32	Zwickau		Germany
52	52	Bellinzona	Tessin	Switzerland	6500
53	38	Aarau		Switzerland
54	37	Bern		Switzerland	3010
55	24	Chur		Switzerland
56	36	Lausanne		Switzerland
57	58	Luzern		Switzerland	6000
58	26	Winterthur		Switzerland
59	25	Zürich		Switzerland

Sponsors and Collaborators

• Pierre Fabre Pharma GmbH
• Pierre Fabre Pharma Austria
• Pierre Fabre Pharma AG

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pierre Fabre Pharma GmbH
• ClinicalTrials.gov Identifier: NCT04045691
• Other Study ID Numbers: NIS-PFO-2019-1921
• First Posted: Aug 5, 2019
• Last Update Posted: Jan 19, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Pierre Fabre Pharma GmbH: BERING; Encorafenib; Binimetinib
• Additional relevant MeSH terms: Melanoma

Study Results

No Results Posted as of Jan 19, 2021